Process for producing methoxyiminoacetamide compounds and intermediates

ABSTRACT

A compound of the formula [I]: ##STR1## wherein X is hydrogen, lower alkyl, lower alkoxy or halogen; ˜is any configuration of E-isomer, Z-isomer or a mixture thereof is produced by reacting a compound of the formula [II] ##STR2## wherein X and ˜are as defined above; W is --CN or --COOR; and R is a lower alkyl, with methylamine in the presence of methanol. The compound [I] is useful for an agricultural fungicide. An intermediate used for producing the compound [I] is also disclosed.

FIELD OF THE INVENTION

The present invention relates to a process for producingmethoxyiminoacetamide compounds of the formula: ##STR3## wherein X ishydrogen, lower alkyl, lower alkoxy or halogen; and ˜ is anyconfiguration of E-isomer, Z-isomer or a mixture thereof, which areuseful as agricultural fungicides, and intermediates used for theproduction of the compounds of the formula [I].

BACKGROUND OF THE INVENTION

The compounds of the formula [I] are novel compounds which have beendisclosed for the first time in EP-A-398 692 in the name of the presentassignee, and they are considered to be remarkably useful compounds asagricultural fungicides having excellent fungicidal activities againstmicroorganisms such as Piricularia oryzae, Pellicularia sasakii,Pseudoperonospora cubensis and the like.

In the above application, the compounds of the formula [I] are producedby several routes. However, at this time, the present inventors havefound other novel synthetic routes for producing the compounds of theformula [I] which are more economical with minimum by-products.

OBJECTS OF THE INVENTION

One object of the present invention is to provide a novel process forproducing the methoxyiminoacetamide compounds of the formula [I] whichare useful for agricultural fungicides.

Another object of the present invention is to provide a novelintermediate used in the process of the present invention.

These objects as well as other objects and advantages of the presentinvention will become apparent to those skilled in the art from thefollowing description.

SUMMARY OF THE INVENTION

According to the present invention, the compound of the above formula[I] is produced by reacting a compound of the formula [II]: ##STR4##wherein X and ˜ are as defined above; W is --CN or --COOR; and R islower alkyl, with methylamine in the presence of methanol. The compoundof the formula [II] is produced by methylating a compound of the formula[III]: ##STR5## wherein X, R and ˜ are as defined above; Y is --CN,--COOH or --COOR; and M is hydrogen or an alkali metal, with a compoundof the formula:

    CH.sub.3 --L                                               [IV]

wherein L is halogen or --OSO₂ OCH₃.

Alternatively, the compound of the formula [I] is produced bymethylating a compound of the formula [V]: ##STR6## wherein X, M and ˜are as defined above with a compound of the formula:

    CH.sub.3 --L                                               [IV]

wherein L is halogen or --OSO₂ OCH₃.

Among the compounds of the formula [II], the compounds wherein Z is--CN, i.e., the compounds of the formula [II']: ##STR7## wherein X and ˜are as defined above, have not been disclosed heretofore in the priorart and are novel compounds. Thus, the present invention also providesthe compounds of the formula [II']. The compounds of the formula [II']are produced by methylating a compound of the above formula [III]wherein Y is --CN, i.e., a compound of the formula [III']: ##STR8##wherein X, M and ˜ are as defined above, with a compound of the aboveformula [IV].

DETAILED DESCRIPTION OF THE INVENTION

In each compound disclosed in the present specification, examples of the"lower alkyl" represented by X include alkyl having 1 to 6 carbon atoms,preferably 1 to 4 carbon atoms, for example, methyl, ethyl, propyl,isopropyl, butyl, isobutyl, t-butyl and the like. Examples of the "loweralkoxy" include alkoxy having 1 to 6 carbon atoms, preferably 1 to 4carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, t-butoxy and the like. Examples of "halogen" includefluorine, chlorine, bromine and iodine. Examples of the "lower alkyl"represented by R include the same groups as those described with respectto the above X. Examples of the alkali metal include potassium, sodiumand the like. Examples of "halogen" represented by L include the samehalogen atoms as those described with respect to the above X.

According to the process of the present invention, the compound of theformula [I] can be obtained by introducing 1 to 10 moles of methylaminegas into 1 mole of the compound of the formula [II] in a solvent such asa lower alcohol (e.g. methanol, ethanol, etc.), water, acetone,acetonitrile, benzene, toluene, methylene chloride, chloroform or thelike with or without an organic base such as triethylamine, pyridine orthe like, or by reacting the compound of the formula [II] with asolution of methylamine in methanol or water under normal pressure or ina sealed tube at 0° to 150° C. for 15 minutes to 24 hours.

The compound of the formula [II] can be obtained by methylating theoxime compound of the formula [III] with the compound of the formula[IV]. For example, the methylation can be conducted in a solvent such asdimethylformamide, dimethylsulfoxide, benzene, toluene, acetone,tetrahydrofuran or a mixed solvent thereof at -20° to 120° C. for 15minutes to 5 hours in the presence of a base such as potassiumcarbonate, sodium carbonate, potassium hydroxide, sodium hydroxide,sodium hydride, potassium t-butoxide, sodium methylate, sodium ethylateor the like. In general, for methylation of oximes, a lot of nitron issometimes formed depending upon reaction conditions. However, accordingto this reaction, the amount of by-products is very small and thedesired compound of the formula [II] is obtained in a good yield.Particularly, when the compound of the formula [III] wherein Y is --COOHis used, the desired compound which can be used for the reaction of thenext step without any purification such as that by column chromatographycan be obtained.

Optionally, the compound of the formula [II] can be converted intoanother corresponding compound of the formula [II] by a known method,for example, conversion of a nitrile into an ester.

Alternatively, the compound [I] can be directly obtained by methylatingthe compound of the formula [V] with the compound [IV]. This methylationcan be conducted according to the same manner as that described aboveand the compound of the formula [I] can be obtained in a good yieldwithout purification such as that by column chromatography.

Optionally, the compound of the formula [I] thus obtained wherein X ishydrogen can be converted into a corresponding compound of the formula[I] wherein X is lower alkyl or halogen by a known method such asalkylation or halogenation.

As described above, the compound of the formula [II'] is a novelcompound and can be obtained by methylating the compound of the formula[III'] with the compound of the formula [IV] according to the samemanner as that described above.

The compounds of the formulas [I] to [II] are present as E-isomer orZ-isomer, or a mixture thereof.

Regarding the compound of the formula [I], its E-isomer and Z-isomer canbe represented by the following formulas: ##STR9## wherein X and W areas defined above.

The compound of the formula [VI]: ##STR10## wherein A is --CONHCH₃ or--COOR, i.e., Z-isomer wherein W is --CONHCH₃ or --COOR can be convertedinto E-isomer of the formula [VII]: ##STR11## by treating it with anacid in a lower alcohol. For example, the treatment can be conducted byreacting the compound of the formula [VI] with 0.1 to 10 moles of anacid such as hydrogen chloride, sulfuric acid or toluenesulfonic acid ina lower alcohol under normal conditions or a sealed tube at 20° to 150°C. for 15 minutes to 48 hours. Further, this reaction can also beapplied to a reaction mixture containing both compounds of the formulas[VI] and [VII] as well as crude products.

The compounds of the formulas [III] and [III'] which are used asstarting compounds in the present invention can be produced, forexample, from a known 2-phenoxyphenylacetonitrile compound (U.S. Pat.No. 4,198,418) or 2-phenoxybenzylaldehyde compound (Japanese PatentPublication No. 50204/1983) as described in the Reference Exampleshereinafter. Further, the compound of the formula [IV] is known as amethylating agent.

The compound of the formula [I] thus obtained can be purified, ifnecessary, according to a conventional method, for example, columnchromatography and can be used as a agricultural fungicide according toa known method.

As described above, according to the present invention, there isprovided a novel process for producing methoxyiminoacetamide compoundswhich are useful as agricultural fungicides and the process of thepresent invention is economical with minimum by-products.

The following Examples and Reference Examples further illustrate thepresent invention in detail but are not to be construed to limit thescope thereof.

EXAMPLE 1 Production of2-methoxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide (mixture of E- andZ-isomers)

To α-methoxyimino-2-phenoxyphenylacetonitrile (a mixture of E- andZ-isomers) (0.50 g, 0.002 mole) were added methanol (1 ml) and 40%aqueous solution of methylamine (3.11 g, 0.01 mole) and the mixture wasreacted in a sealed tube at 100° C. for 18 hours. After completion ofthe reaction, water was added to the reaction mixture, followed byextraction with methylene chloride. The extract was dried over anhydrousmagnesium sulfate and concentrated under reduced pressure, and then theresulting residue was purified by silica gel chromatography (ethylacetate/n-hexane) to obtain2-methoxyimino-N-methyl-2-2-phenoxyphenyl)acetamide (0.15 g, yield:26.4%) as a colorless oil.

¹ HNMR (CDCl₃) δ ppm: 2.79 (d, 1.75H, J=4.9Hz), 2.87 (d, 1.25H,J=4.9Hz), 3.91 (s, 1.75H), 4.01 (s, 1.25H), 6.32 (br, s, 0.58H), 6.64(br, s, 0.42H), 6.85-7.61 (m, 9H)

EXAMPLE 2 Production ofE-2-methoxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide

To E-α-methoxyimino-2-phenoxyphenylacetatic acid methyl ester (17.12 g,0.06 mole) were added anhydrous methanol (60 ml) and 40% methylaminesolution in methanol (13.98 g, 3.0 equivalents) and the mixture washeated under reflux for 40 minutes. After completion of the reaction,the reaction mixture was concentrated under reduced pressure and theresulting residue was purified by silica gel chromatography (ethylacetate/n-hexane). The crystals thus obtained were recrystallized fromethyl acetate/n-hexane to obtainE-2-methoxyimino-N-methyl-2-(2-phenoxyphenyl)-acetamide (12.21 g, 71.6%) as colorless prisms (melting point: 82°-83° C.).

¹ HNMR (CDCl₃) δ ppm: 2.87 (d, 3H, J=5.0Hz), 3.91 (s, 3H), 6.65 (br, s,1H), 6.87-7.38 (m, 9H)

REFERENCE EXAMPLE 1 Production of E-α-methoxyimino-2-phenoxyphenylaceticacid methyl ester

To E-α-methoxyimino-2-phenoxyphenylacetonitrile (a mixture of E- andZ-isomers) (0.76 g, 0.003 mole) was added 30% hydrochloric acid inmethanol (4.5 ml) and the mixture was stirred under reflux for 22 hours.After completion of the reaction, 8% aqueous solution of sodiumbicarbonate (100 ml) was added to the reaction mixture and extractedwith methylene chloride. The extract was dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The resulting residuewas purified by silica gel chromatography (ethyl acetate/n-hexane) toobtain E-α-methoxyimino-2-phenoxyphenylacetic acid methyl ester (0.40 g,46.7%) as colorless crystals (melting point: 109°-110° C.).

¹ HNMR (CDCl₃) δ ppm: 3.78 (s, 3H), 4.03 (s, 3H), 6.86-7.48 (m, 9H)

EXAMPLE 3 Production of E-α-methoxyimino-2-phenoxyphenylacetic acidmethyl ester

To a solution of E-α-hydroxyimino-2-pheoxyphenylacetic acid (10.00 g,0.0389 mole) in dimethyl sulfoxide (50 ml) and toluene (50 ml) was addedsodium methoxide (4.83 g, 0.0894 mole) with stirring under ice cooling,and the mixture was stirred at room temperature for 20 minutes and thencooled. Dimethylsulfate (11.28 g, 0.0894 mole) was added at 6°-18° C.over 6 minutes, followed by stirring at room temperature for 4.5 hours.After completion of the reaction, conc. hydrochloric acid (1.2 ml) andwater (100 ml) were added to the reaction mixture with stirring underice cooling, followed by extraction with toluene. The extract was washedwith water and concentrated under reduced pressure, and then theresulting residue was recrystallized (methanol) to obtainE-α-methoxyimino-2-phenoxyphenylacetic acid methyl ester (8.11 g, yield:73.1%) as colorless crystals (melting point: 107°-109° C.). ¹ HNMR(CDCl₃) δ ppm: 3.78 (s, 3H), 4.03 (s, 3H), 6.86-7.46 (m, 9H)

EXAMPLE 4 Production of E-α-methoxyimino-2-phenoxyphenylacetic acidmethyl ester

To E-α-hydroxyimino-2-pheoxuphenylacetic acid (1.29 g, 0.005 mole) wereadded dried dimethylformamide (10 ml) and 85% potassium hydroxide (0.73g, 0.011 mole) and the mixture was stirred at room temperature for 15minutes. Dried toluene (10 ml) was added to the mixture, to which wasfurther added dropwise dimethylsulfate (1.39 g, 0.011 mole) under icecooling. After completion of the addition, the mixture was stirred atroom temperature for 1.5 hours. Then, ether (100 ml) was added, followedby washing with water three times. The ether layer was dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresulting residue was purified by silica gel chromatography (ethylacetate/n-hexane) to obtain E-α-methoxyimino-2-phenoxyphenylacetic acidmethyl ester (1.20 g, yield: 84.1%) as colorless crystals (meltingpoint: 109°-110° C.).

¹ HNMR (CDCl₃) δ ppm: 3.78 (s, 3H), 4.03 (s, 3H), 6.86-7.46 (m, 9H)

EXAMPLE 5 Production of E-α-methoxyimino-2-(4-methylphenoxy)phenylaceticacid methyl ester

E-α-hydroxyimino-2-(4-methylphenoxy)phenylacetic acid (0.87 g, 0.32mole) was dissolved in dried dimethylformamide (6.4 ml). To the solutionwas added 85% potassium hydroxide (0.51 g, 0.0077 mole). Afterdissolving with heating, dried toluene (6.4 ml) was added. Under icecooling, dimethylsulfate (0.97 g, 0.0077 mole) was added dropwise andthe mixture was stirred at room temperature for 1.5 hours.

After completion of the reaction, water (50 ml) containing conc.hydrochloric acid (1 ml) was added to the reaction mixture and extractedwith ether (50 ml). The ether layer was washed in turn with water (50ml) and 4% aqueous solution of sodium bicarbonate (30 ml), dried overanhydrous sodium sulfate and concentrated under reduced pressure, andthen the resulting residue was purified by silica gel chromatography(ethyl acetate/n-hexane) to obtainE-α-methoxyimino-2-(4-methylphenoxy)phenylacetic acid methyl ester (0.75g, yield: 78.1%) as a colorless oil.

¹ HNMR (CDCl₃) δ ppm: 2.32 (s, 3H), 3.79 (s, 3H), 4.04 (s, 3H),6.85-7.39 (m, 8H)

EXAMPLE 6 Production of E-α-methoxyimino-2-phenoxyphenylacetic acidmethyl ester

To E-α-hydroxyimino-2-phenoxyphenylacetic acid methyl ester (1.09 g,0.004 mole) were added dried dimethylformamide (6 ml) and potassiumhydroxide (0.29 g, 0.0044 mole) and the mixture was stirred at roomtemperature for 15 minutes. Then, dried toluene (6 ml) was added to themixture, to this was further added dropwise dimethylsulfate (0.61 g,0.0044 mole) under ice cooling. After completion of the addition, themixture was stirred at room temperature for 2 hours. Then, ether (100ml) was added, followed by washing with water three times. The etherlayer was dried over anhydrous magnesium sulfate and concentrated underreduced pressure. The resulting residue was purified by silica gelchromatography (ethyl acetate/n-hexane) to obtainE-α-methoxyimino-2-phenoxyphenylacetic acid methyl ester (1.20 g, yield:80.6%) as colorless crystals (melting point: 109°-110° C.).

¹ HNMR (CDCl₃) δ ppm: 3.78 {s, 3H), 4.03 (s, 3H), 6.86-7.46 (m, 9H)

According to the same manner as that described above, each compound wasproduced under the following reaction conditions with varying a base andmethylating agent, respectively.

                                      TABLE 1                                     __________________________________________________________________________    Example                                                                            Base  Methylating   Reaction  Yield                                      No.  (eq.) agent (eq.)                                                                          Solvent                                                                              conditions                                                                              (%)                                        __________________________________________________________________________    7    60% NaH                                                                             Me.sub.2 SO.sub.4                                                                    THF    0° C., 60 minutes                                                                96.5                                            (1.1) (1.2)                                                              8    t-BuOK                                                                              Me.sub.2 SO.sub.4                                                                    THF    0° C., 30 minutes                                                                82.4                                            (1.3) (1.2)                                                              9    KOH   MeI    DMF/PhMe                                                                             Room temperature,                                                                       66.6                                            (1.1) (1.2)         2 hours                                              __________________________________________________________________________     Note:                                                                         Me: methyl; tBu: tbutyl; THF: tetrahydrofuran; DMF: dimethylformamide;        PhMe: toluene                                                            

EXAMPLE 10 Production ofE-α-methoxyimino-2-(4-methylphenoxy)phenylacetic acid methyl ester

E-α-hydroxyimino-2-(4-methylphenoxy)pheylacetic acid methyl ester (0.71g, 0.0025 mole) was dissolved in dried tetrahydrofuran (10 ml), followedby the addition of 60% sodium hydride (0.13 g, 0.033 mole). Then, themixture was stirred at room temperature for 20 minutes and to this wasadded dropwise a solution of dimethylsulfate (0.44 g, 0.0035 mole)dissolved in dried THF (2.5 ml) under ice cooling, followed by stirringfor 1.75 hours under ice cooling. After completion of the reaction,water was added to the reaction mixture which was adjusted to pH 1 withconc. hydrochloric acid. The mixture was extracted twice with methylenechloride, dried over anhydrous sodium sulfate and concentrated underreduced pressure. The resulting residue was purified by silica gelchromatography (ethyl acetate/n-hexane) to obtainE-α-methoxyimino-2-(4-methylphenoxy)phenylacetic acid methyl ester (0.61g, yield: 81.3%) as a colorless oil.

¹ HNMR (CDCl₃) δ ppm: 2.32 (s, 3H), 3.79 (s, 3H), 4.04 (s, 3H),6.85-7.39 (m, 8H)

EXAMPLE 11 Production of α-methoxyimino-2-phenoxyphenylacetonitrile (amixture of E- and Z-isomers)

To α-hydroxyimino-2-phenoxyphenylacetonitrile (a mixture of E- andZ-isomers) (1.19 g, 0.005 mole) were added dried dimethylformamide (10ml) and potassium carbonate (0.90 g, 0.0065 mole), and dimethylsulfate(0.76 g, 0.006 mole) was added dropwise to the mixture under icecooling, followed by stirring at room temperature for 1.5 hours. Aftercompletion of the reaction, ether (150 ml) was added, followed bywashing twice with water (100 ml). The ether layer was dried overanhydrous magnesium sulfate and concentrated under reduced pressure, andthen the resulting residue was purified by silica gel chromatography(ethyl acetate/n-hexane) to obtainα-methoxyimino-2-phenoxyphenylacetonitrile (1.13 g, yield: 89.6%) as acolorless oil.

¹ HNMR (CDCl₃) δ ppm: 4.03 (s, 0.7H), 4.17 (s, 2.3H), 6.89-7.67 (m, 9H)

EXAMPLE 12 Production of α-methoxyimino-2-phenoxyphenylacetonitrile (amixture of E- and Z-isomers)

To α-hydroxyimino-2-phenoxyphenylacetonitrile (a mixture of E- andZ-isomers) (1.19 g, 0.005 mole) were added dried dimethylformamide (10ml) and potassium carbonate (0.90 g, 0.006 mole), and methyl iodide(0.78 g, 0.0055 mole) was added dropwise to the mixture under icecooling, followed by stirring at room temperature for 4 hours. Aftercompletion of the reaction, ether (150 ml) was added, followed bywashing twice with water (100 ml). The ether layer was dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresulting residue was purified by silica gel chromatography (ethylacetate/n-hexane) to obtain α-methoxyimino-2-phenoxyphenylacetonitrile(1.06 g, yield: 84.0%) as a colorless oil.

¹ HNMR (CDCl₃) δ ppm: 4.03 (s, 0.7H), 4.17 (s, 2.3H), 6.89-7.69 (m, 9H)

EXAMPLE 13

Production of α-methoxyimino-2-(4-chlorophenoxy)phenylacetonitrile (amixture of E- and Z-isomers)

α-hydroxyimino-2-(4-chlorophenoxy)phenylacetonitrile (a mixture of E-and Z-isomers) (1.36 g, 0.005 mole) was dissolved in drieddimethylformamide (10 ml) and potassium carbonate (0.90 g, 0.0065 mole)was added to the mixture. Further, dimethylsulfate (0.76 g, 0.006 mole)was added to the mixture under ice cooling, followed by stirring at roomtemperature for 1 hour. Then, ether (150 ml) was added to the mixture,which was washed twice with water. The ether layer was dried overanhydrous magnesium sulfate and concentrated under reduced pressure, andthen the resulting residue was purified by silica gel chromatography(ethyl acetate/n-hexane) to obtainα-methoxyimino-2-(4-chlorophenoxy)phenylacetonitrile (1.35 g, yield:94.4%) as a pale yellow oil.

¹ HNMR (CDCl₃) δ ppm: 4.02 (s, 0.69H), 4.17 (s, 2.31H), 6.90-7.68 (m,8H)

EXAMPLE 14 Production of E2-methoxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide

To E-2-hydroxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide (10.00 g,0.037 mole) were added acetone (200 ml), potassium carbonate (15.34 g,0.111 moles) and dimethylsulfate (9.33 g, 0.074 moles) and the mixturewas stirred at room temperature for 9 hours. After completion of thereaction, the reaction mixture was filtered, washed with acetone andconcentrated under reduced pressure. The oil thus obtained was dissolvedin toluene (50 ml) and to this was added an aqueous 1N sodium hydroxidesolution (50 ml), followed by stirring at room temperature for 30minutes. The mixture was extracted with toluene, washed with water andconcentrated, and then the resulting residue was recrystallized(methanol/water) to obtainE-2-methoxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide (9.93 g, yield:94.4%) as colorless crystals (melting point: 81.5°-83° C.).

¹ HNMR (CDCl₃) δ ppm: 2.87 (d, 3H, J=5.0Hz), 3.91 (s, 3H), 6.65 (br, s,1H), 6.87-7.38 (m, 9H)

EXAMPLE 15 Production ofE-2-methoxyimino-N-methyl-2-[2-(4-methylpheoxy)phenyl]acetamide

E-2-hydroxyimino-N-methyl-2-[2-(4-methylphenoxy)phenyl]acetoamide (1.00g, 0.0035 mole) was dissolved in dried acetone (7 ml), and potassiumcarbonate (0.63 g, 0.0046 mole) and dimethylsulfate (0.53 g, 0.0042mole) were added to the mixture, which was reacted at room temperaturefor 22 hours. After completion of the reaction, water was added to thereaction mixture, which was extracted twice with methylene chloride,dried over anhydrous sodium sulfate and concentrated under reducedpressure. The resulting residue was purified by silica gelchromatography (ethyl acetate/n-hexane) to obtainE-2-methoxyimino-N-methyl-2-[2-(4-methylphenoxy)phenyl] -acetamide ascolorless crystals (0.96 g, yield: 92.3%).

¹ HNMR (CDCl₃) δ ppm: 2.29 (s, 3H), 2.81 (d, 3H, J=4.9Hz), 3.89 (s, 3H),6.71 (br, s, 1H), 6.82 (d, 1H, 'J=8.1Hz), 6.89-6.92 (m, 2H), 7.05-7.10(m, 3H), 7.23-7.31 (m, 2H)

REFERENCE EXAMPLE 2 Production ofE-2-hydroxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide

To crude E-α-hydroxyimino-2-phenoxyphenylacetic acid methyl ester (39.6g, 0.0747 mole, purity: 51.2%) were added methanol (100 ml) and 40%aqueous solution of methylamine (15.45 g, 0.199 mole) and the mixturewas stirred at room temperature for 15 hours. Then, 40% aqueous solutionof methylamine (7.73 g, 0.0995 mole) was added to the mixture which wasstirred in an oil bath at 70° C. for 6 hours. After completion of thereaction, water (200 ml) and toluene (100 ml) were added to the reactionmixture, which was stirred with ice cooling for one hour. Theprecipitated crystals were filtered off and recrystallized(methanol/toluene) to obtainE-2-hydroxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide (12.31 g, yield:60.1%) as colorless crystals (melting point: 183°-184.5° C.).

¹ HNMR (d₆ -DMSO₄) δ ppm: 2.65 (d, 3H, J=4.5Hz), 6.30-7.47 (m, 9H), 7.92(q, 1H, J=4.5Hz)

REFERENCE EXAMPLE 3 Production ofE-2-hydroxyimino-N-methyl-2-[2-(4-methylphenoxy)phenyl]acetamide

E-α-hydroxyimino-2-(4-methylphenoxy)phenylacetic acid methyl ester (1.00g, 0.0035 mole) was dissolved in methanol (7 ml) and 40% methylaminesolution in methanol (0.54 g, 0.007 mole) was added to the mixture,which was refluxed for 70 minutes. A 40% methylamine solution inmethanol (1.36 g, 0.0175 mole) was further added to the mixture, whichwas refluxed for 3 hours. After completion of the reaction, the reactionmixture was concentrated under reduced pressure to giveE-2-hydroxyimino-N-methyl-2-[2-(4-methylphenoxy)phenyl]acetamide (1.00g, yield: 100.0 %) as an amorphous.

¹ HNMR (CDCl₃) δ ppm: 2.31 (s, 3H), 2.86 (d, 3H, J=5.9Hz), 6.60 (br, s,1H), 6.84-7.36 (m, 8H), 7.93 (br, s, 1H).

REFERENCE EXAMPLE 4 Production of E-α-hydroxyimino-2-phenoxyphenylaceticacid

To E-α-hydroxyimino-2-phenoxyphenylacetic acid methyl ester (9.99 g,0.0368 mole) were added methanol (36.8 ml), sodium hydroxide (3.23 g,0.081 mole) and water (36.8 ml) and the mixture was heated under refluxfor one hour. After heating, conc. hydrochloric acid (1 ml) was added tothe mixture under ice cooling and the precipitated crystals werefiltered off and recrystallized (methanol/ethyl acetate/n-hexane) toobtain E-α-hydroxyimino-2-phenoxyphenylacetic acid (6.90 g, yield:72.9%) as colorless crystals (decomposition: 180° C.).

1HNMR (d₆ -DMSO₄) δ ppm: 6.83-7.38 (m, 9H), 12.26 (br, s, 1H), 12.85(br, s, 1H)

REFERENCE EXAMPLE 5 Production ofE-α-hydroxyimino-2-(4-methylphenoxy)phenylacetic acid

To E-α-hydroxyimino-2-(4-methylphenoxy)phenylacetic acid methyl ester(1.00 g, 0.0035 mole) were added methanol (3.5 ml), water (3.5 ml),sodium hydroxide (0.31 g, 0.0077 mole) and the mixture was heated underreflux for one hour. After cooling to room temperature, the resultantwas adjusted to pH 1 with 5% of hydrochloric acid. After stirring atroom temperature, the crystals were filtered off and washed with waterto obtain colorless crystals ofE-α-hydroxyimino-2-(4-methylphenoxy)phenylacetic acid (0.90 g, yield:94.7%).

¹ HNMR (d₆ -DMSO₄) δ ppm: 2.27 (s, 3H), 6.78-7.37 (m, 8H)

REFERENCE EXAMPLE 6 Production ofα-hydroxyimino-2-phenoxyphenylacetonitrile (a mixture of E- andZ-isomers)

To anhydrous ethanol (15 ml) was dissolved sodium (0.55 g, 0.024 mole)and a mixture of 2-phenoxyphenylacetonitrile (4.18 g, 0.02 mole) andanhydrous ethanol (3 ml) was added dropwise to the mixture below 0° C.over 7 minutes. Isoamyl nitrite (3.51 g, 0.03 mole) was further addeddropwise to the mixture below 0° C. over 10 minutes, followed bystirring at room temperature for 24 hours. After completion of thereaction, 5% hydrochloric acid was added to the reaction mixture, whichwas extracted with ether and dried over anhydrous magnesium sulfate. Thecrude product obtained by concentration under reduced pressure waspurified by silica gel chromatography (ethyl acetate/n-hexane) to obtainα-hydroxyimino-2-phenoxyphenylacetonitrile (4.53 g, yield: 95.1%) ascrystals having a low melting temperature.

¹ HNMR (CDCl₃) δ ppm: 6.83-7.67 (m, 9H), 8.68 (br, s, 0.25H), 9.02 (br,s, 0.75H)

REFERENCE EXAMPLE 7 Production ofα-hydroxyimino-2-(4-chlorophenoxy)phenylacetonitrile (a mixture of E-and Z-isomers)

To anhydrous ethanol (25 ml) was added metallic sodium (0.97 g, 0.042mole), and after dissolution, a solution of2-(4-chlorophenoxy)phenylacetonitrile (8.53 g, 0.035 mole) in anhydrousethanol (7 ml) was added dropwise to the mixture. Then, isoamyl nitrite(6.15 g, 0.0525 mole) was added dropwise to the mixture. After reactionat room temperature for 2.5 hours, water was added to the reactionmixture, which was adjusted to pH 1 with conc. hydrochloric acid,extracted with ether, washed with water and dried over anhydrousmagnesium sulfate.

Ether was concentrated under reduced pressure and the resulting residuewas purified by silica gel chromatography (ethyl acetate/n-hexane) toobtain α-hydroxyimino-2-(4-chlorophenoxy)phenylacetonitrile (9.03 g,yield: 94.6%) as a light brown viscous liquid.

¹ HNMR [CDCl₃) δ ppm: 6.90-7.68 (m, 8H), 9.12 (br, s, 0.28H), 9.46 (br,s, 0.72H)

REFERENCE EXAMPLE 8 Production of H-α-hydroxyimino-2-phenoxyphenylaceticacid

To α-hydroxyimino-2-phenoxyphenylacetonitrile (a mixture of E- andZ-isomers) (0.71 g, 0.003 mole) were added ethanol (3 ml), potassiumhydroxide (0.40 g, 0.0072 mole) and water (3 ml). After completion ofthe reaction, methylene chloride (10 ml) and 10% hydrochloric acid wereadded to the reaction mixture, and the crystals ofα-hydroxyimino-2-phenoxyphenylacetic acid precipitated were filtered offto obtain colorless crystals (0.47 g, yield: 60.9%).

¹ HNMR (d₆ -DMSO₄) δ ppm: 6.83-7.38 (m, 9H), 12.26 (br, s, 1H), 12.85(br, s, 1H)

REFERENCE EXAMPLE 9 Production of 2-phenoxybenzaldoxime

To 2-phenoxybenzaldehyde (4.96 g, 0.025 mole) were added anhydrousmethanol (50 ml) and hydroxylamine hydrochloride (2.08 g, 0.03 mole),and the mixture was stirred at 60° C. for 3 hours. After completion ofthe reaction, water (200 ml) was added to the reaction mixture, whichwas extracted with methylene chloride and dried over magnesium sulfate.The crude product obtained by concentration under reduced pressure waspurified by silica gel chromatography (ethyl acetate/n-hexane) to obtain2-phenoxybenzaldoxime (3.95 g, yield: 74.1%) as a colorless oil.

¹ HNMR (CDCl₃) δ ppm: 6.88-7.41 (m, 8H), 7.45 (s, 1H), 7.86 (dd, 1H,J=7.9., 2.0), 8.49 (s, 1H)

EXAMPLE 16 Production of α-methoxyimino-2-phenoxyphenylacetonitrile (amixture of E- and Z-isomers)

To 2-phenoxybenzaldoxime (1.07 g, 0.005 mole) was added dried ether (10ml), and chlorine (0.46 g, 0.0065 mole) was introduced into the mixturebelow -10° C., followed by stirring at 0° C. for 5 hours. After thecompletion of the reaction, the reaction mixture was concentrated underreduced pressure, and then, dried methylene chloride (10 ml) andtetraethylammonium cyanide (0.86 g, 0.0055 mole) were added to theresulting residue and the mixture as stirred overnight. After completionof the reaction, water (150 ml) was added to the reaction mixture, whichwas extracted with methylene chloride, dried over anhydrous magnesiumsulfate and purified by silica gel chromatography (ethylacetate/n-hexane) to obtain crudeα-hydroxyimino-2-phenoxyphenylacetnitrile (0.51 g), to which were addeddried dimethylformamide (4 ml) and potassium carbonate (0.36 g, 0.0026mole). Dimethyl sulfate (0.30 g, 0.0024 mole) was further added to themixture, which was stirred at room temperature for 2 hours. Aftercompletion of the reaction, ether (100 ml) was added to the reactionmixture, which was washed twice with water, dried over anhydrousmagnesium sulfate and concentrated under reduced pressure. The crudeproduct thus obtained was purified by silica gel chromatography (ethylacetate/n-hexane) to obtain α-methoxyimino-2-phenoxyphenylacetnitrile(0.21 g, yield: 16.6%) as a colorless oil.

¹ HNMR (CDCl₃) δ ppm: 4.03 (s, 0.7H), 4.17 (s, 2.3H), 6.89-7.67 (m, 9H)

EXAMPLE 17 Production of E-α-methoxyimino-2-phenoxyphenylacetic acidmethyl ester

To 1.62 M solution of n-butyllithium in hexane (500 ml, 0.81 mole) wereadded dropwise a mixture of diphenyl ether (206.81 g, 1.215 moles) anddried tetrahydrofuran (405 ml) below 5° C. over 40 minutes and themixture was stirred at room temperature for 24 hours. After completionof the reaction, the reaction mixture was added dropwise to a stirringsolution of dimethyl oxalate (118.09 g, 1.215 moles) in driedtetrahydrofuran (810 ml) below 0° C. over 50 minutes, followed bystirring at room temperature for 24 hours.

After completion of the reaction, ice-water (2 liters) was added to themixture, which was extracted with toluene (500 ml) and the extract waswashed with water. Then, the solution was dried over anhydrous sodiumsulfate and concentrated under reduced pressure to obtain a brown oil(302.94 g). To this oil were added methanol (1.3 liters) andhydroxylamine hydrochloride (47.25 g, 0.68 mole) and the mixture washeated under reflux for one hour, and then, a solution of sodiumhydroxide (79.2 g, 1.98 moles) in water (450 ml) was further added tothe mixture, which was heated under reflux for one hour. Aftercompletion of the reaction, methanol was distilled off under reducedpressure, followed by the addition of water (1.8 liters) and furtherwashing twice with methylene chloride (1 liter). Then, conc.hydrochloric acid was added to the aqueous layer until pH became lowerthan 2 and the crystals precipitated were filtered off to obtain crudecrystals of E-α-hydroxyimino-2-phenoxyphenylacetic acid (141.55 g,yield: 68.0% from n-butyllithium). To the crude crystals (25.73 g, 0.1mole) thus obtained were added dried dimethylformamide (150 ml) and 85%potassium hydroxide (14.52 g, 0.22 mole), and the mixture was heated toobtain a solution. Then, dried toluene was added to the solution, anddimethyl sulfate (27.75 g, 0.22 moles) was added dropwise at 25° to 30°C. over 5 minutes and the mixture was stirred at room temperature for1.5 hours. After completion of the reaction, 1% hydrochloric acid (700ml) was added to the reaction mixture, which was extracted with toluene(500 ml), and then, the extract was washed with an aqueous 2% sodiumbicarbonate solution and dried over anhydrous sodium sulfate. The crudeproduct obtained by concentration under reduced pressure was purified byrecrystallization (methanol) to obtainE-α-methoxyimino-2-phenoxyphenylacetic acid methyl ester (21.15 g,yield: 74.1%) as colorless crystals (melting point: 109°-110° C.).

¹ HNMR (CDCl₃) δ ppm: 3.78 (s, 3H), 4.03 (s, 3H), 6.86-7.46 (m, 9H)

EXAMPLE 18 Production of E-α-methoxyimino-2-phenoxyphenylacetic acidmethyl ester

To Z-α-methoxyimino-2-phenoxyphenylacetic acid methylester acid VI'(0.29 g, 1.0 mmole) were added dried methanol (3 ml) and 10%hydrochloric acid solution in methanol (0.36 g, 1.0 mmole) and themixture was heated under reflux for 6 hours to conduct isomerization.

The reaction mixture was concentrated under reduced pressure, giving acrystalline residue (0.29 g). The residue consists of E-isomer andZ-isomer in the ratio of 77.6:22.4, by a ¹ H-NMR measurement.

EXAMPLE 19 Production ofE-2-methoxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide

To Z-2-methoxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide VI" (0.28 g,1.0 mmole) were added dried methanol (3 ml) and 10% hydrochloric acidsolution in methanol (0.36 g, 1.0 mmole) and the mixture was heatedunder reflux for 6 hours to conduct isomerization.

The reaction mixture was concentrated under reduced pressure, giving acrystalline residue (0.28 g.). The residue consists of E-isomer andZ-isomer in the ratio of 91.5:8.5, by a ¹ H-NMR measurement.

What is claimed is:
 1. A compound of the formula [II']: ##STR12##wherein X is hydrogen, lower alkyl, lower alkoxy or halogen; and ˜ isany configuration of E-isomer, Z-isomer or a mixture thereof.
 2. Acompound according to claim 1, wherein X is hydrogen or methyl.